The inhibitory effects of ML264 on osteosarcoma cells are likely mediated via inhibition of JAK2 and STAT3 phosphorylation, decrease in β‐catenin and Runx2 levels, down‐regulation of cyclin D1, cyclin E1, CDK4, N‐cadherin, vimentin, Snail and MMPs expression, and up‐regulation of E‐cadherin levels. This evidence concerns the gene RUNX2 and osteosarcoma.